Civilian and combat trauma to limbs often results in serious injuries to the peripheral nerves that cause significant morbidity. Advances in trauma management have significantly reduced overall mortality; however, patients are left with significant disability and morbidity due to peripheral nerve injuries. There is an acute need for reliable measures to monitor nerve injury and repair to make informed management decisions in clinic. Currently, noninvasive techniques that allow early assessment of regeneration in traumatic nerve injuries are not available in clinical practice. We propose to develop and validate non-invasive magnetic resonance (MR) based diffusion tensor imaging (DTI) technology, to monitor the degenerative and regenerative response in the nerves after traumatic injuries. We hypothesize that alterations in DTI parameters can detect nerve fiber degeneration and regeneration. Our preliminary studies in animals support our hypothesis that this technique can measure Wallerian-like degeneration and regeneration in the injured nerves. We show that normal human nerves can be imaged with this technology supporting the feasibility of this project. The gaps in knowledge in this area include lack of: a) normative DTI parameters for different peripheral nerves; and b) studies demonstrating utility of DTI technology to detect peripheral nerve degeneration and regeneration in humans. Our specific Aims are: 1) To establish in vivo DTI-based techniques of imaging intact peripheral nerves in humans; and 2) To establish in vivo DTI-based techniques of imaging peripheral nerve degeneration and regeneration in traumatic peripheral nerve disorders in humans. The goals of the proposed studies are to collect normative data in controls and apply it to patients with complete nerve injuries (Sunderland grade V) undergoing nerve repairs. The principle reason to focus on patients with complete nerve injury and nerve repair in this initial project evaluating DTI technology is that in this clinical situation maximal change in DTI parameters is expected because of complete denervation and subsequent reinnervation of the distal nerve stumps, which will allow setting up thresholds of DTI parameters in individual nerves. DTI parameters will be correlated with currently used clinical, electrodiagnostic, and histological (when available) measures to assess nerve regeneration. Validation of DTI technology in patients with complete nerve injuries will allow broader application of this modality in patients with different grades of traumatic nerve injuries in clinic. We anticipate that this technology will facilitate medical management decisions in these patients. These studies are likely to establish thresholds for different DTI parameters in controls and completely denervated nerve segments, which will provide important range of comparative data with potential applicability to non-traumatic neuropathic conditions to monitor nerve degeneration and regeneration. PUBLIC HEALTH RELEVANCE: Civilian and combat trauma to limbs often results in serious injuries to the peripheral nerves that cause significant morbidity. Presently non-invasive clinical investigative techniques do not exist that allow accurate measurement of extent of nerve injury and natural responses of repair/healing. This project proposes to develop magnetic resonance imaging (MRI) technology to assess the extent of nerve injury and repair in patients with traumatic nerve injuries.